TEMA 1.

ENGINYERIA BIOQUÍMICA I BIOTECNOLOGIA

BIOTECHNOLOGY

The application of science and technology to living

organisms, as well as parts, products and models
thereof, to alter living or non-living materials for the
production of knowledge, goods and services (OECD)

the use of biological processes and technology-to solve

problems or make useful products.

BIOTECHNOLOGY WORLD MARKET

VALUE: 58 BILLION $ (2000)

pollution control

20% 0% energy
27%
chemicals
metal recovery
agriculture
15% health care
17% food
14% 7%

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World Biotechnology Market Value (2000-2004)

Year US$(Billion) % Growth

2001 78.1
2002 88.1 12.9
2003 101.0 14.7
2004 112.6 11.5
2005 126.3 12.2

World Biotechnology Market Segmentation –2005

Category % Share
Medical 61.5
Agriculture and food 12.2
Industry & environment 4.2
Other 22.1


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World Biotechnology Market Value (2000-2004)

Year US$(Billion) % Growth

2001 78.1
2002 88.1 12.9
2003 101.0 14.7
2004 112.6 11.5
2005 126.3 12.2

World Biotechnology Market Segmentation –2005

Category % Share
Medical 61.5
Agriculture and food 12.2
Industry & environment 4.2
Other 22.1

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 A nivel mundial incrementa la importancia de la
biotecnología ..

$90 86 12%

$80 Sales - biologics

73 10%
% market

ket
$70 8,5%

% of the pharma mark

62
7,9%
Sales (billions)

$60 7,3% 8%
6,8% 53
6,4%
$50 6,0%
45
5,3% 6%
$40 4,9% 38
4,3% 33
3,7% 3,8% 3,9% 29
$30 3,3% 3,5% 25
4%
2,9%
21
$20 17
15
12 2%
8 9 10
$10 6 7
5
$0 0%
92 93 94 95 96 97 98 99 00 01 02 03 04 05 06 07 08 09 10
Source: Ernst & Young. Global Biotechnology Report, 2006

• Biotechnology sector (world-wide) growing at rates above 15% since 1992 and
expected to continue growing at rates > 10% in the next four years
• Biologics gaining importance, with sales expected to reach $86bn in 2010
• Biologics market share as % of the pharma market has more than doubled in
the last 10 years, from under 4% in 1997 to 8.5% in 2006

What's wellspring—a
Biotech’s fueling thesurvey
biotech
of theengine—2010 2 tosector
health of the private 20113in 2014
Nature Biotechnology, 29, 1083–1089 (2011)

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10
 SITUACION Y TENDENCIAS DE
LA BIOTECNOLOGIA ESPAÑOLA
• Las empresas que
generan el 30% del
Industria
PIB encuentran en la
F
Farmacéutica
é ti bi t
biotecnología
l í un
Industria importante aliado:
Energía
Química
• Como fuente
imprescidible de
innovación en
Agricultura productos y servicios
Industria
Ganadería
(en el caso de la
Alimentaria biotecnología sanitaria)
30-40%
Y pesca .
del PIB
• Como herramienta
clave para reactivar
sectores maduros
Sector
(cómo en el caso de la
Medio Minería alimentación)
Ambiente
Sector • Como alternativa
Cuero, Tecnologías sostenible a costosos
procesos productivos
Textil Sanitarias

• En los próximos años se producirán nuevos Fármacos en el mercado

avances fruto de la convergencia entre
biotecnología, nanotecnología y TICs Biotech
20%

• P di i
Predicciones sobre
b nuevas aprobaciones
b i en
función del estado de desarrollo del pipeline
mundial
Conventional
80%

Previsión de aprobaciones biotech en la FDA Fármacos en desarrollo

50
45
40
Biotech
35 50%
Otros
30
Vacunas
25 recombinantes Conventional
20 A. Monoclonales 50%
15
Fuente: Comisión Europea, FDA
10
5
0
2006 72007 2008 2009
Fuente: Athur D. Little para France Biotech

6 1
11
 El sector biotec español ha crecido sustancialmente en pocos años

But still has a long way to go!

• With a growth rate of >20%*, Spain’s biotech sector is growing is currently

growing four times as fast as the EU average and much faster than the US
biotech industry
• Nevertheless, Spain’s market is still only ≈ ¼ the size of the US market!
• Given the substantial difference in size, it is expected that both biotech
markets will take at least another 30 – 35 years to converge

Convergence with the US market

Spain USA
Source: Genoma España and Nature Biotechnology, volume 24

7 4
12
Distribución geográfica de las compañías biotecs españolas

…datos relevantes de la situación biotec

8 5
13
Distribución de las empresas que realizan actividades relacionadas con la
biotecnología

9 6
14
 10
7
15
 biotechnology techniques

biotechnology techniques
DNA/RNA: (Genomics) pharmacogenomics, gene
probes, genetic engineering, DNA/RNA
sequencing/synthesis/amplification, and use of
antisense technology. Gene and RNA vectors:
gene therapy, viral vectors.

Proteins and other molecules:

(Proteomics)
Sequencing/synthesis/engineering of
proteins and peptides; improved delivery
methods for large molecule drugs; protein
isolation and purification, signaling,
identification of cell receptors.

11
16
2
 biotechnology techniques

Nanobiotechnology: Applies the tools

and processes of nano/microfabrication
to build devices for studying biosystems
and applications in drug delivery,
diagnostics etc.

Bioinformatics: Construction of
databases on genomes, protein
sequences; modelling complex
biological processes, including systems
biology.

biotechnology techniques
Cell and tissue culture and engineering:
Cell/tissue engineering (including tissue
scaffolds and biomedical engineering),
cellular fusion (hybridoma),
vaccine/immune stimulants, embryo
manipulation.

Process biotechnology techniques:

Fermentation using bioreactors,
bioprocessing, bioleaching, biopulping,
biobleaching, biodesulphurisation,
bioremediation, biofiltration and
phytoremediation. Cell/tissue culture

12
17
3
1.2. Enginyeria Bioquímica

Biochemical engineering
is concerned with conducting biological processes
on an industrial scale providing the link between
biology and chemical engineering (Aiba, 1973)

Role of the biochemical engineer

• Translate new biological discoveries into practical processes

• Improvement of existing processes
• Operation of existing processes in production plants

Why to use a bioprocess ?

Less energy is consumed

Decrease the use of raw
materials and water
Can simplify processes Reduces cost
Create new materials Reduces pollution
Products can be more safe
Less waste

13
18
4
1.2. Enginyeria Bioquímica

organism

selection
mutation
genetic engineering

selection waste
raw downstream
pretreatment biocatalysts
material sterilization
processing
products

air,
energy

biocatalysts
enzymes

microorganisms

animal cells

plant cells

14
19
5
1.2. Enginyeria Bioquímica

Characteristics of a bioprocess

• Raw materials are renewable resources

• Mild reaction conditions: pH, temperature,
pressure
• Low products concentration
• High reaction specificty
• Biocatalyst variability

high
bioprocess
technology

medium

low

15
20
6
1.2. Enginyeria Bioquímica

Bio-gas Bio-ethanol

energy
biofuels
Bio-diesel Bio-hydrogen

mineral
recovery

bio-leaching

CuSO4
CuFeS2 Fe2(SO4)3

Acidothiobacillus

17
21
7
1.2. Enginyeria Bioquímica

environmental

acrylamide 100,000 tonnes

a year (Mitsubishi Rayon)

chemical Natureworks® polylactide

polymer,140,000 tonnes a
year (Cargill-Dow)

Sorona® 3GT™ fiber. includes

Bio-PDO™ corn-derived 1,3-
propanediol (DuPont)

18
22
8
1.3. Aplicacions d'enzims, microorganismes i cèl·lules. Nous productes.

Enzymes

Phytic acid = inositol hexaphosphate

(IP6) = phytate

Phytate contents in plants

19
23
9
1.3. Aplicacions d'enzims, microorganismes i cèl·lules. Nous productes.

myo-inositol-hexaphosphate phosphohydrolase
3-phytase EC 3.1.3.8 (Aspergillus niger)
6-phytase EC 3.1.3.26 (Peniophora lycii)

introduced into market in 1991

Monogastric animals lack phytate degrading enzymes

Phosphorus is not bioavailable
Pollution: phytate-P excreted
bioavailability insoluble chelate of minerals (Ca, Zn, Mg, Fe)
digestibility: phytate–protein or starch complexes

thermo-stability fungal phytase

lower pH optimum

Expression of a bacterial phytase gene in the salivary gland ¡

food

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1.3. Aplicacions d'enzims, microorganismes i cèl·lules. Nous productes.

L-lysine: 850,000 tonnes

L-glutamic acid: 1,300 tonnes

Aspartame

plant growth stimulants

agriculture bio-pesticides

Mycoherbicide

Collego® (1980): living

spores of the fungus
Colletotrichum
gloeosporioides which
infects and kills
northern jointvetch.

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1.3. Aplicacions d'enzims, microorganismes i cèl·lules. Nous productes.

● Mass propagation of plant clones

● Genetically modified crops
• Plant breeding or modifications to improve
resistance to pests, diseases, drought and salt
conditions
• Modification of plants to improve nutritional and
processing characteristics

Pharmacological
agents
Steroids

Antitumor
agents

health
care Antibiotics

Vitamins

Vaccines

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1.3. Aplicacions d'enzims, microorganismes i cèl·lules. Nous productes.

● Drug delivery systems

● Gene therapy
● Genotyping Test
● Vaccines manufactured by plants and animals
● Tissue engineering / replacement organs

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1.3. Aplicacions d'enzims, microorganismes i cèl·lules. Nous productes.

BIOPHARMACEUTICALS
biopharmaceutical industry

Naturally occurring or modified polypeptide, protein, DNA or RNA

product -produced by recombinant DNA or hybridoma technology and
expressed in cell lines or transgenic animals or plants- that is to be
used for therapeutic, prophylactic or in vivo diagnostic use in humans

growth factors
hormones
human proteins: interferons...
monoclonal antibodies
vaccines
medical diagnostic test

Total sales and sales growth trend in the US

biotech market for biologic drugs (2003–2008)
Nature Biotechnology 27, 987- 993 (2009)
What's fueling the biotech engine—2008

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1.3. Aplicacions d'enzims, microorganismes i cèl·lules. Nous productes.

ANY producte aplicació

1982 insulina diabetis
1985 hormona del creixement dèficit Hormona creixement
1986 α interferon tricoleucemia
1986 ortoclone (MAB) rebuig trasplantament renal
1986 vacuna hepatitis B hepatitis B
1987 tPA infart miocardi
1989 eritropoyetina anèmia
1989 factor VIII hemofília
1993 dornasa (DNAsa) fibrosi quística
1998 trastuzumab càncer de mama

Top nine categories of biologic drugs in terms of US sales in 2008

US sales of these drug categories.

The table shows the growth rates
of the categories between 2007
and 2008. The red boxes indicate
the major categories showing the
fastest growth rate during that
period

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1.3. Aplicacions d'enzims, microorganismes i cèl·lules. Nous productes.

1931
fertilized chicken’s
eggs could be used
for virus cultivation

flu viruses
are injected

The entire process takes at least six months

A single vaccine dose requires one egg

90 million doses manufactured in Europe each year

Vaccines from cells

VERO (kidney epithelial cells from an African green monkey)
MDCK (Madin-Darby Canine Kidney Cells)
16 weeks for a finished vaccine
less risk of contamination by bacteria or viruses
cell cultures are also suitable for aggressive flu viruses
non chicken protein allergy
the capacity can be adapted more easily to the actual demand

Production plant for vaccines

on the basis of cell
cultures.(Novartis Behring)

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1.4. Fermentació

MICROBIAL FERMENTATION
Alcoholic
beverages
Dairy products
Vinegar
Fermentation
inoculated with Thermometer
previous product Pre-1900 Heat exchangers
Pure yeast cultures for No quality control
beer (1896)
Batch

Wooden barrels
Copper
Shallow trays
Trickle filters

MICROBIAL FERMENTATION
Bakers’ yeast
citric, lactic acids
glycerol, acetone/butanol

pH electrodes
temperature
Pure cultures 1900-1940 control

Batch
Fed batch
Feed

Steel vessels
Air spargers
Mechanical
stirring

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1.4. Fermentació

MICROBIAL FERMENTATION
antibiotics
gibberilin
aminoacids
nucleotides
steroids

pH and oxygen
Mutation and selection
programmes
1940-1960 electrodes
Control loops

batch
feed
fed batch
continuous

Mechanically
aerated vessels
Aseptic
operation

ENZYMES/MICROBIAL FERMENTATION / CELL CULTURE

SCP
enzymes
aminoacids
xanthan
MABs

Genetic engineering of Computer linked

production strains
1960-1980 control

batch
feed
fed batch
continuous

immobilization
animal cell
culture

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1.4. Fermentació

ENZYMES/MICROBIAL FERMENTATION / CELL CULTURE

Biopharmaceuticals
chymosin
bovine somatotropine

Recombinant products Computer linked

1980-present control

batch
feed
fed batch
continuous
immobilization
animal cell
culture
Racemic
resolution

http://bio.org/
http://www.bio-economy.net/index.html
http://www.biocat.cat/home/biocat-3/en/
http://www.efb-central.org/

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